Solid calcium deposits, urinary calculi and kidney stones have been a significant medical problem for many years. Despite recent progress in sonic disruption of stones, safe chemical treatment and prevention are still preferred. Current chemical therapy utilizes potassium citrate or magnesium administration to prevent calcium stone formation (Johansson et al., J. Urology, 124: 770-774, 1980; Preminger et al., ibid. 134:20-23, 1985; Pak et al., ibid. 134:11-19, 1985).
Methionine has been prescribed for control of urinary pH in dogs and cats and has been effective in reducing the occurrence of both bladder and kidney stones in dogs (Thornton, Current Vet. Therapy IV, 695-702, 1971). dl-Methionine is effective in cats to maintain the urinary pH at 6 (Rich, Current Vet. Therapy IV, 703-706, 1971).
Differences exist in the relative effectiveness of methionine compounds and other chemicals especially in sulfhydryl reducing substances. These differences may be attributed to the control mechanisms that operate in animals and man to regulate the amounts of these substances wherein giving more of a substance does not significantly increase blood and tissue levels of that substance. Stegink, J. Nutrition, 116:1185-1192, 1986, showed that 0.5 gm of methionine elevated total blood methionine two-fold for 2 hours with 1-methionine but three-fold for 4 hours with d-methionine.
Regarding human nutrition, 1-methionine is an essential amino acid whereas d-methionine is not essential. For purposes of metabolism, 1-methionine via S-adenosylmethionine has an important methylating function. In this function it loses a methyl group from its sulfur atom to become homocysteine. Homocysteine, as is known, when in excess can lead to homocysteinuria and may in excess be disease associated.
Cuperus, Arthritis and Rheumatism, 28: 1128-1233, 1985, describes a feature of inflamed synovial fluid, such as that occurring in arthritis patients, as the accumulation of polymorphonuclear (PMN) leukocytes. One function of the leukocytes is the destruction of invading elements such as microorganisms. For this destruction, the leukocyte releases hydrogen peroxide and enzymes, e.g., myeloperoxidase, into the extracellular fluid. In the presence of hydrogen peroxide and chloride ion, myeloperoxidase catalyzes the formation of reactive hypochlorous acid (HOCl) which can oxidize tissue components and plasma protease inhibitors. Oxidation and subsequent inactivation of these protease inhibitors in vivo may lead to unrestrained proteolysis, resulting in severe tissue damage. dl-Methionine is available as a one-a-day food supplement in 500-mg. oral tablet form. The normal serum level of methionine in man is 15 ppm.
Different species utilize d-forms of amino acids to different extents. Humans and monkeys utilize d-methionine poorly while pigs, dogs, rabbits, chickens and rats utilize d-methionine as a sulfur source fairly well. Animals do not metabolize N-blocked-d-methionine as they do N-blocked-1-methionine. Some N-blocking groups are not cleaved by enzymes that remove common blocking groups such as acetyl groups (Cho, J. Parenteral and Enteral Nutrition, 4: 544-547, 1980; Stegink, J. Nutr. 110: 42-49, 1980; Rotruck, J. Nutr. 105: 331-337, 1975.)
The Scheinberg U.S. Pat. No. 4,315,028 describes a method of treatment of arthritis employing substituted cysteines.
U.S. Pat. No. 3,952,115 describes foodstuffs containing N-acyl 1-methionine esters and N-acyl 1-cysteine esters.
There is a need at present for means of treating disease conditions presenting as solid calcium deposits, calculi, kidney stones, hypocalcemia, hypercalcemia, urinary calcium and the like (for normal calcium values and methodology, and incorporated herewith, refer to Tietz, Clinical Chemistry, 901 et seq. and 1015 et seq., Saunders Co., 1976).
It is therefore an object of the present invention to provide compositions for consumption or administration and treatment, for normalizing calcium metabolism and alleviating disease conditions of the kind described.
It is also an object of the invention to provide methods for normalizing calcium metabolism and alleviating these disease conditions.
It is a further object of the invention to provide means for preventing or alleviating symptoms of homocysteinuria that may result from excess methionine intake.
These and other objects, features and advantages will be seen from the following detailed description of the invention.